Cyclosporine-A (CsA) and its analogues have been shown to be neuroprotective in experimental models of neurological disorders, including Parkinson&#8217;s disease (PD) and stroke. Because CsA does not easily cross the blood brain barrier (BBB), a high dose (i.e., > 10 mg/kg in rats) and chronic administration of the drug may be necessary to produce beneficial effects. However, immunosuppressant side effects are associated with such a high dose CsA regimen. Recently, the bradykinin receptor, Cereport (also called RMP-7), has been shown to transiently increase permeability of the BBB. In the present study, we examined the effects of co-administration of CsA and Cereport in the unilateral 6-OHDA model of PD. Animals were pretreated with vehicle, CsA alone (1 mg/kg, a low dose that does not produce immunosuppression) or CsA in combination with Cereport (9 ug/kg). At one month post-lesion, amphetamine-induced rotational tests revealed that lesioned animals that received either vehicle infusion only (controls) or CsA alone exhibited 244?52 and 229?40 (mean ? S.E.) full turns over 30 mins, respectively, while animals that received CsA + Cereport displayed 78?26 mean rotations. Similarly, elevated body swing tests revealed that lesioned animals that received either vehicle infusion only or CsA alone exhibited 92.5?10 and 95?7.5 (mean ? S.E.%) biased swings, respectively, whereas lesioned animals that received CsA + Cereport displayed 55?12.5% mean biased responses. Differences in both motor behaviors, between vehicle or CsA alone and CsA + Cereport, were statistically significant. Histological analyses using TH immunohistochemistry supported the observed attenuation of 6-OHDA-induced behavioral abnormalities. Near complete depletions of nigral TH-ir neurons were noted in lesioned animals that received vehicle infusion or CsA alone. In contrast, lesioned animals that received CsA + Cereport exhibited a 50-70% sparing of nigral TH-ir neurons. Similar observations were noted in striatal TH-ir fiber density. These results suggest that Cereport permitted the protective effects of low dose CsA to be manifested. The safe and effective administration of combined CsA and Cereport offers a novel way of producing protective effects in the central nervous system without the toxic liabilities of high dose CsA.